Any hopes Bristol-Myers Squibb Co. and AstraZeneca PLC had that type 2 diabetes drug Onglyza (saxagliptin) could pick up steam have been wiped out now that a Phase IV post-marketing study showed the drug was not superior to a placebo in helping provide cardiovascular protection to patients.

The topline results of the CV outcomes study, dubbed SAVOR (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus), were announced June 19, The trial achieved the primary safety endpoint of non-inferiority when Onglyza was compared to a placebo, but failed to reach a primary efficacy endpoint of superiority.

The Phase IV study was designed to test whether treatment with Onglyza, compared with placebo, will reduce incidences of cardiovascular death, non-fatal myocardial infarction or non-fatal ischemic stroke. In pre-approval research, Onglyza was not associated with an increased risk of cardiovascular effects. In fact, pooled results suggested a cardio-protective effect, prompting the post-marketing study.

Further data from the trial is still being evaluated by the companies and will be announced at the European Society of Cardiology Congress in September. The companies did not release any of the individual results of the study at this time and did not comment on any safety aspects, including pancreatitis – a known issue with the drug. The study included 16,500 patients and took place in 25 countries. Patients included in the trial had type 2 diabetes and a history of cardiovascular disease or related risk factors.

Onglyza is a dipeptidyl peptidase-4 (DPP-4) inhibitor that was approved in July 2009 Also see "AstraZeneca/Bristol's Diabetes Drug Onglyza Cleared" - Pink Sheet, 31 July, 2009..

Status Quo

The results of SAVOR were not a surprise to anyone; analysts had largely written off any positive outcomes from the study and therefore did not expect any commercial bump due to the outcome. While results of the study will not generate any positive sales trends for Onglyza, it is unlikely it will impact sales negatively either.

“We view this as a mildly disappointing result, albeit we and consensus had not factored in the upside to sales had this study shown an unequivocally positive result,” wrote Deutsche Bank analyst Mark Clark in a June 19 note to investors.

“We believe these results are generally in line with investor expectations. We also do not expect a finding of non-inferiority to change physician prescribing habits (although a finding of superiority would certainly have to the upside),” noted ISI Group analyst Mark Schoenebaum.

Onglyza has long been the ugly stepsister in the DPP-4 class of diabetes drugs. Bristol/AstraZeneca’s DPP-4 was second to market after Merck & Co. Inc.’s Januvia (sitagliptin) launched in 2006, and has never come close to having the same blockbuster potential – it brought in $709 million in 2012 compared with Januvia’s $4 billion. Januvia sales are expected to grow to as much as $6.5 billion by 2018, according to analysts’ consensus projections, while Onglyza is not expected to reach $1 billion in annual sales until 2020.

Onglyza has been a disappointment since its launch. Bristol CEO Lamberto Andreotti commented in May 2010, “We were expecting a deeper sales uptake, also counting on faster growth of the DPP-4 class that has not happened.” Also see "For Bristol, Onglyza Disappoints And Health Care Reform Takes A Toll" - Pink Sheet, 3 May, 2010.

DPP-4s have seen a mild reception on the market. The class is generally less effective than some other alternatives, but it does have the appeal of a largely benign safety profile and oral administration. Yet, the diabetes category is becoming overcrowded with other classes of drugs, such as GLP-1 agonists and SGLT2 inhibitors, which offer greater efficacy and provide patients with help managing their weight.

But uptake of the class has not been a problem for market-leading Merck, which currently has no other diabetes products on the market Also see "Merck And Pfizer Make A Late Play For The Diabetes Market" - Pink Sheet, 29 April, 2013.. The Januvia franchise brought in north of $5 billion in revenues in 2012 and includes Januvia, Janumet (a combination of Januvia and metformin), and Juvisync (a combination of Januvia and the cholesterol drug simvastatin). The N.J. pharma is also developing a once-weekly DPP-4 inhibitor that is chemically unique from Januvia.

Several other manufacturers of DPP-4 drugs are also conducting CV outcomes studies; SAVOR was the first to report, but Merck is expected to have results from the 14,000-patient TECOS study of Januvia in 2014. Takeda Pharmaceutical Co. Ltd. is expected to have results from its 5,400-patient EXAMINE study of Nesina (alogliptin) before the end of the year and Eli Lilly & Co. and partner Boehringer Ingelheim GMBH will present data from its 6,000-patient CAROLINA study of Tradjenta (linagliptin) in 2018 Also see "Lilly/BI Report Success For Oral Diabetes Drug, Adjust Alliance" - Pink Sheet, 7 January, 2013..

“Doctors are expected to read across from SAVOR (both efficacy and safety) to other DPP-4 drugs,” noted Schoenebaum.

Nothing To SAVOR For Bristol/AZ From Phase IV Results

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